Mechanical Anisotropy in Crystalline Saccharin - ACS Publications

Sep 1, 2010 - ABSTRACT: The nanoindentation technique has been employed to relate the mechanical properties of saccharin single crystals with their ...
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DOI: 10.1021/cg1009362

Mechanical Anisotropy in Crystalline Saccharin: Nanoindentation Studies

2010, Vol. 10 4650–4655

M. S. R. N. Kiran,† Sunil Varughese,‡ C. Malla Reddy,§ U. Ramamurty,*,† and Gautam R. Desiraju*,‡ †

Department of Materials Engineering, Indian Institute of Science, Bangalore 560 012, India, Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India, and § Indian Institute of Science Education and Research, Kolkata, Mohanpur 741 252, India ‡

Received July 15, 2010; Revised Manuscript Received August 18, 2010

ABSTRACT: The nanoindentation technique has been employed to relate the mechanical properties of saccharin single crystals with their internal structure. Indentations were performed on (100) and (011) faces to assess the mechanical anisotropy. The load-displacement (P-h) curves indicate significant differences in the nature of the plastic deformation on the two faces. The P-h curves obtained on the (011) plane are smooth, reflecting homogeneous plasticity. However, displacement bursts (pop-ins) are observed in the P-h curves obtained on the (100) plane suggesting a discrete deformation mechanism. Marginal differences exist in the hardness and modulus on the two faces that may, in part, be rationalized, although one notes that saccharin has a largely three-dimensional close-packed structure. The structural origins of the fundamentally different deformation mechanisms on (100) and (011) are discussed in terms of the dimensionality of the hydrogen bonding networks. Down the (100) planes, the saccharin dimers are stacked and are stabilized by nonspecific van der Waals interactions mostly between aromatic rings. However, down the (011) planes, the molecules are stabilized by more directional and cross-linked C-H 3 3 3 O hydrogen bonds. This anisotropy in crystal packing and interactions is reflected in the mechanical behavior on these faces. The displacements associated with the pop-ins were found to be integral multiples of the molecule separation distances. Nanoindentation offers an opportunity to compare experimentally, and in a quantitative way, the various intermolecular interactions that are present in a molecular crystal.

Introduction The control of mechanical properties of molecular solids is a particularly challenging aspect of crystal engineering and design.1-3 Compared to other classes of materials such as metals, ceramics, and polymers, the structural basis for the mechanical behavior of crystalline organic solids is poorly understood.4-6 The lack of information on elastic and plastic deformation responses and, in general, the absence of systematic investigations at the molecular level may be attributed to the difficulty in preparing samples, the nonavailability of suitable characterization techniques, and the complex nature of the crystal structures themselves. Consequently, materials scientists and crystal engineers need, in many cases, to take a trial-and-error approach; this is very often the case in the pharmaceutical industry.7,8 The recent advent of the nanoindentation technique, wherein loads and displacements can be measured with resolutions of 1 nN and 0.2 nm, respectively, has allowed for the evaluation of the mechanical behavior of extremely small-scale systems such as thin films and small single crystals.9-13 In recent times, this technique has also been utilized to study relatively soft materials such as organic and metal-organic compounds.14 Although the mechanical performance of these solids, per se, is not of major import as they are not loadbearing materials, it is of significance in the context of their manufacture and usage. For example, many organic compounds that are used in the pharmaceutical industry have to be crushed and ground during tableting, and a correlative *To whom correspondence should be addressed. E-mail: desiraju@ sscu.iisc.ernet.in (G.R.D.); [email protected] (U.M). pubs.acs.org/crystal

Published on Web 09/01/2010

understanding of their hardness and toughness is important.8,15-17 A stronger tablet is produced when the contact area between particles is increased and when the compound has a lesser resilience. Nanoindentation also facilitates the probing of crystal anisotropy, which in turn provides new perspectives on supramolecular bonding that is intrinsic to the crystal. Realization of these attributes has been a recent phenomenon, and only a few papers have appeared that employ nanoindentation in organic crystals.18-25 For example, Ramos et al.26,27 attempted to investigate the mechanical behavior of sucrose and RDX crystals using nanoindentation. Roberts et al.28-31 examined the correlation between the indentation hardness and modulus in organic solids. Sun and co-workers correlated the compaction behavior and plastic deformation on nanoindentation to the crystal packing in theophylline, methyl gallate, and the 1:1 co-crystal of these compounds.32 Sweetening agents such as sucrose, acesulfame potassium, aspartame, and sodium saccharinate dihydrate are extensively used in chewable tablet formulations to mask unpleasant tastes and to facilitate pediatric dosing. While selecting a sweetener, one must consider drug-excipient compatibility, patient acceptability, and manufacturability.33 Although some studies on the physical and chemical properties of these organic compounds are available in the open literature, their mechanical properties, which are important from the manufacturing perspective, have not been examined. Saccharin, 1,1-dioxo-1,2-benzothiazol-3one, the acid precursor of sodium saccharinate, has a closepacked structure and is a representative system for a variety of brittle molecular crystals used in the pharmaceutical industry. Also, saccharin (pKa 2.2) has been used as an acid co-former (salt former) to modify the solubility of a drug and to enhance r 2010 American Chemical Society

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Figure 1. Saccharin (a) indexed crystal faces; (b) view of interactions in the (011) plane. (c) Oblique arrangement of molecules with respect to the (100) plane. (d) View of molecular arrangement along (001) plane. The indentation direction (a*) is represented by the arrowhead. (e) Stacking of molecules in the [100] direction.

the bioavailability of active pharmaceutical ingredients (APIs).34 In this paper, we have examined the mechanical properties of crystalline saccharin with nanoindentation. Experimental Section Large single crystals (1  1  0.5 cm) of saccharin were grown from commercially available material (Loba Chemie, India) by slow evaporation of a saturated solution of EtOH at room temperature over a period of 3-4 weeks. The crystals were harvested and dried quickly using soft tissue paper and were washed with paraffin oil to remove any small crystals that might have stuck to the surface of larger crystals. Crystals were of rhombic shape with major (100) and (011) faces. The crystals were firmly mounted on a stud using cyanoacrylate glue before nanoindentation. Around six or seven crystals were mounted on different faces and used in several experiments. The ability to obtain large single crystals greatly assisted in the mounting and subsequent experimentation. The experiments were performed on the (100) and (011) faces with a nanoindenter (Triboindenter of Hysitron, Minneapolis, USA) with an in situ imaging capability. The machine continuously monitors and records the load, P, and displacement, h, of the indenter with force and displacement resolutions of 1 nN and 0.2 nm, respectively. A cube-corner diamond indenter with a tip radius of ∼75 nm was used to indent the crystals. In order to identify flat regions for the experiment, the crystal surfaces were imaged prior to indentation using the same indenter tip. A loading rate of 0.2 mN/s and a hold time of 10 s at peak load were employed. A minimum of 10 indentations were performed on each crystallographic face. The indentation impressions were captured immediately after unloading, so as to avoid time-dependent elastic recovery of the residual impression.

The P-h curves were analyzed using the standard Oliver-Pharr method10,35 to extract the elastic modulus, E, of the crystal in that orientation. However, this method was not employed for estimation of the hardness, H, as there was significant plastic flow during indentation, which resulted in pile-up of material against the indenter. Such pile-up, when present, makes the estimation of H using the O-P method inaccurate.36 Therefore, H was determined from the maximum indentation load, Pmax, divided by the contact area, A. The latter was estimated from images of the indentation impressions.

Results and Discussion Saccharin crystallizes in the monoclinic space group P21/c (a = 9.472(1), b = 6.923(1), c = 11.732(1) A˚, β = 103.20(1)o, V = 748.982 A˚3, Z = 4) with (100) and (011) as major faces.37 The representation of the crystal morphology with the indexed faces is given in Figure 1a. The attachment energy, Eatt, is the energy released on the attachment of a growth-slice to a growing crystal face. Thus, Eatt = Elatt - Eslice, where Elatt is the lattice energy of the crystal and Eslice is the energy released on the formation of a growth-slice of a thickness equal to the interplanar d-spacing for the crystallographic plane that represents a face. The interplanar spacings (d) are 9.22 and 5.92 A˚ for the (100) and (011) orientations, respectively. The Eatt are, respectively, -15.858 and -27.790 kJ/mol for the (100) and (011) faces. The Dreiding 2.21 force field38 was used to calculate the attachment energies of the various crystal faces of saccharin using Materials Studio 4.4. The powder X-ray diffraction pattern (Cu-KR) of saccharin was generated from

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Figure 2. Representative P-h curves of saccharin of obtained with indentation normal to (100) and (011) planes. Arrows indicate discrete displacement bursts or pop-ins.

the single crystal structure using Mercury and the interplanar d-spacings were calculated. Representative P-h curves obtained on the two different faces of saccharin crystals are shown in Figure 2. Both plots show large residual depths upon unloading, which indicates that the crystal undergoes significant plastic deformation during indentation. While the loading part of the P-h curve obtained on the (011) face is smooth, several distinct displacement bursts were seen in the P-h curve obtained on the (100) face. An interesting observation is that plastic deformation was observed on both faces even when they were indented to an extremely small load of 0.01 mN, which corresponds to a depth of ∼12 nm. This is because of the sharp geometry of the indenter tip, which causes the indented material to undergo plastic deformation. Average values of H and E are 0.610 ( 0.01, 13.36 ( 0.05 GPa for (100) and 0.550 ( 0.02, 14.01 ( 0.03 GPa on (011). The error bars correspond to the standard deviations on the 10 measurements that were made on each face. The slight difference (∼5%) in the moduli of both the crystal faces suggests marginal anisotropy in the interaction characteristics. On the other hand, the degree of anisotropy in H is more significant, with (100) harder by ∼10% as compared to (011), suggesting possible differences in the micromechanisms of plasticity; these are discussed below. The first displacement burst in the P-h curve, obtained on (100), is ∼18 nm in magnitude; the load at which it occurs is consistent at 0.5 ( 0.1 mN. Interestingly, the magnitude of the displacements associated with the pop-ins, hpop-in, appear to occur in integer multiples of 18 nm. An atomic force microscopy (AFM) image of the indent made on the (100) plane with a Pmax of 6 mN is shown in Figure 3a, and a crosssectional profile is shown in Figure 3c. The latter shows discrete slip steps, whose heights range between ∼18 and 54 nm, consistent with the size of the pop-ins detected in the P-h curves. At large loads (∼5 mN), cracking along one of the edges of the indenter was noted (Figure 3a) with a concomitantly large displacement burst of ∼214 nm. Note that this is also close to an integer multiple of 18 (216). The fracture toughness (Kc) of the crystal was estimated by using the crack length measured using the AFM software and the expressions given by Laugier39,40 for cube-corner indents, to be 0.02 ( 0.002 MPa m0.5. Wendy et al.18 have estimated

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fracture toughness of several organic crystals, such as sucrose, adipic acid, and acetaminophen, and also for NaCl, using the microindentation technique, and their Kc values are 0.08 ( 0.001, 0.02 ( 0.005, 0.05 ( 0.006, and 0.50 ( 0.07 MPa m0.5, respectively. The estimated brittleness index, H/Kc, of saccharin is 3.0  103 m-0.5, which is comparable to that of ice (2.8  103 m-0.5). The fracture parameters of the other organic crystals listed above are also comparable to those of saccharin and ice. This is reasonable because all these crystals are characterized by a three-dimensional arrangement of hydrogen bonds.17 Interestingly, no cracking was observed on (011) when indented to the same maximum load of 6 mN (Figure 3c), suggesting that there is considerable anisotropy in the mechanical performance of saccharin in terms of plastic deformation and fracture behavior. Images of the indents on both the faces show material pileup along the edges of the indenter. This is due to the incompressible plastic deformation of material from beneath the indenter to the top surface along the edges of the indenter. The AFM topographic images of both the orientations and their corresponding cross-sectional profiles are presented in Figure 4a,c. It is clear from Figure 4b,d that the quantity and shape of the profiles of the material pile-up are strongly dependent upon the crystallographic orientation. Figure 5 shows that the pile-up profile on (011) is smooth, whereas it is highly faceted on (100). The results presented in the preceding section suggest that both plastic deformation and fracture in the (100) orientation of the crystal are connected to crystallographic features. Discrete displacement bursts in the P-h curves have been extensively reported.40-43 They are due either to the nucleation of dislocation loops or their rapid multiplication during the indentation of metallic and inorganic crystals with initially low dislocation densities.10 In amorphous metals, they arise from nucleation of shear bands.44-46 In organic crystals, plastic deformation can be attributed to glide (or slip), twinning and kinking, all in simple shear.47 Plastic deformation by slipping occurs along a specific crystallographic plane when sheets of molecules glide across one another, similar to a stack of playing cards in a deck. Bandyopadhyay et al.47 have reported that plastic deformation is more likely due to twinning for crystals with low symmetry and few slip systems or when plastic deformation is hindered due to unfavorable alignment and under high loading rates. The primary slip plane in organic materials is assumed to be the weakest plane in that the attachment energy on this plane is the least. Accordingly, slip is preferred along this plane. By this token, the pop-ins observed in the (100) orientation are not surprising as slip planes frequently act as cleavage planes.48 The predicted active slip system in the saccharin crystal is (100) [011].49 Centrosymmetric dimers of saccharin stack over one another along [100]. When indenting the (100) face, the molecular stacks are effectively inclined at an oblique angle to the indenter axis, as represented in Figure 1c. In a stack, the molecules are separated by 3.34 and 3.76 A˚ and are stabilized by nondirectional van der Waals (π 3 3 3 π) interactions. Molecules from adjacent stacks are held by C-H 3 3 3 O hydrogen bonds. In the case of the (100) plane, saccharin molecules make a bilayer arrangement with a dimension of 0.9 nm. Only weak interactions persist between the bilayers. These observations allow for the following possible explanation of the pop-ins only on the (100) face. On indenting along [100], the layers of stacked columns do not break continuously; rather, they get compressed through the

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Figure 3. AFM topographical image of saccharin. (a) Formation of cracks along two corners of the indenter on (100) at a Pmax of 6 mN. (b) No radial cracks observed on (011) under the same load. (c) Horizontal cross-section at the center of the residual indent impression of (a). (d) Horizontal cross-section at the center of the residual indent impression of (b).

weakest π 3 3 3 π interactions and possibly with the nucleation of a few defects. In this process, the layers that are compressed rearrange themselves through the nondirectional π 3 3 3 π interactions to release some of the stored elastic strain energy. On further increase of load, the layers finally break away due to the disruption of the relatively stronger C-H 3 3 3 O interactions between the adjacent stacked dimers allowing sudden penetration of the indenter into the sample which get reflected as a pop-in. The fact that the discrete displacements associated with the pop-ins, 18 nm, is an integral multiple of the molecular separation distance of 0.90 nm corroborates this hypothesis. It is instructive to examine the possible causes for the fact that the pop-in displacements typically are 20 times the molecular separation distance (or integral multiples thereof). As mentioned earlier, the tip of the cube-corner indenter is not atomically sharp but has a finite radius of ∼75 nm. It has been well established, through the mechanics analysis of the spherical contact problem, that the maximum shear stress underneath a spherical tip occurs at a depth that is 0.47 times the

radius of the tip.50 Therefore, this will be the origin for shearing of the planes. However, the shearing cannot terminate within the crystal but has to extend all the way to the free surface of the crystal. Thus, the total shear displacement is likely to be ∼35 nm (0.47  75 nm). The next step is to convert this shear displacement into the equivalent indenter displacement, which is given by 35 cos θ nm, where θ is the angle between the slip plane and the loading direction. Since θ = 62.5° in the present case, the indenter displacement is approximately equal to 16.2 nm which, within experimental errors, is equal to the displacement associated with the first pop-in (18 nm). The reader will note that the location of maximum shear stress is derived for an isotropic solid, whereas the crystals examined in this work are anisotropic. Nevertheless, the reasonable agreement between experimental and estimated values suggests that this is possibly the reason for pop-in displacement being multiples of 20 times the molecular separation distance. Further experimental work on other types of single crystals is essential to put this hypothesis on a firmer footing.

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Figure 4. Pile-up in crystalline saccharin upon nanoindentation: (a) and (c) 3-D images of the residual indented impressions after indentation at a Pmax of 1 mN on (100) and (011) planes; (b) and (d) section plots drawn along the corner to the edge of the indenter to show anisotropy in the pile-up formation around the indenter.

Figure 5. 3-D image of residual indented impression obtained from the (100) surface shows large pile-up in a faceted structure around the indenter. The pile-up height is approximately one-third of the penetration depth.

In (011), several weak C-H 3 3 3 O interactions exist (D, d, θ: 3.38 A˚, 2.46 A˚, 161°; 3.17, 2.50, 128; 3.38, 2.55, 145; 3.48, 2.85, 125; 3.70, 2.96, 136) normal to the plane of indentation. The stacked dimers, formed via strong N-H 3 3 3 O interactions (D, d, θ: 2.79, 1.86, 167), run along [011] with an oblique angle and

the adjacent molecules from the dimers criss-cross to form C-H 3 3 3 O interactions in the two other directions. The vector of two adjacent dimers is effectively the indentation direction on the (011) face. Thus, it is anticipated that indenting along (011) would confer more stiffness.51,52 The slightly lower elastic modulus in (100) is also in good agreement with the higher interplanar d-spacing between the (100) planes (d(100)/ d(011) = 1.55).47 Pop-ins are not observed on (011) because there are more slip planes available. The stacked dimers run down this face with an oblique angle to the indenter, allowing multiple gliding paths. Hence, the plastic deformation is homogeneous without any pop-ins. In this context, we note that Ramos et al.26 did not observe any pop-ins in the P-h curves while indenting sucrose crystals; this is because they used a blunt cube-corner tip having an effective radius, R, of 0.96 μm, which is more than 10 times larger than the tip we used in the current study (R = 0.075 μm). In case of indentation along [100], the active slip system (100) is nearly 90° as it is almost parallel to [011]. Hence, the observed H on (011) is marginally lower (∼0.55 GPa) than on (100) (∼0.61 GPa). Concluding Remarks The nanoindentation technique has been employed to relate the mechanical properties of saccharin single crystals in the

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(100) and (011) orientations with the crystal structure. Our results show anisotropy in the plastic deformation and fracture behavior. The nature of the plastic deformation is homogeneous on the (011) plane and may be attributed to the existence of several possible slip systems nearly parallel to the plane of indentation. On the (100) plane, it is discrete because the slip planes have the least attachment energy and act as cleavage planes that are prone to displacement bursts in the P-h curves due to their higher compressibility. Inhomogeneous pile-up around the indenter impressions also indicates that plastic deformation is dependent on crystallographic orientation. At higher loads, cracks are developed on the (100) plane along the corners of the indenter. In an earlier publication, some of us classified organic crystals as being soft or brittle.4-6 The former are characterized by interaction anisotropy, while the latter are isotropic in terms of interaction strengths. The present study quantifies this differentiation with respect to a single compound, saccharin, and shows that interaction anisotropy may be correlated with mechanical properties such as plastic deformation and lack of continuous response to mechanical deformation. Notably, such a correlation between micro and macro level properties has the promise of drawing together scientists from widely different disciplines into the quest for designing organic crystals with pretargeted properties. Finally, nanoindentation of molecular crystals offers the scope to quantify the strengths of intermolecular interactions experimentally and to compare different types of interactions in a direct way. Acknowledgment. M.S.R.N.K. thanks the UGC for a Dr. D. S. Kothari Post-Doctoral Fellowship. S.V. thanks the DST for a Young Scientist Fellowship. C.M.R. thanks the DST for financial support under the Young Scientist scheme. G.R.D. thanks the DST for a J. C. Bose fellowship.

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